Modelling the Self-Assembly of Elastomeric Proteins Provides Insights into the Evolution of Their Domain Architectures

Abstract

Elastomeric proteins have evolved independently multiple times through evolution. Produced as monomers, they self-assemble into polymeric structures that impart properties of stretch and recoil. They are composed of an alternating domain architecture of elastomeric domains interspersed with cross-linking elements. While the former provide the elasticity as well as help drive the assembly process, the latter serve to stabilise the polymer. Changes in the number and arrangement of the elastomeric and cross-linking regions have been shown to significantly impact their assembly and mechanical properties. However, to date, such studies are relatively limited. Here we present a theoretical study that examines the impact of domain architecture on polymer assembly and integrity. At the core of this study is a novel simulation environment that uses a model of diffusion limited aggregation to simulate the self-assembly of rod-like particles with alternating domain architectures. Applying the model to different domain architectures, we generate a variety of aggregates which are subsequently analysed by graph-theoretic metrics to predict their structural integrity. Our results show that the relative length and number of elastomeric and cross-linking domains can significantly impact the morphology and structural integrity of the resultant polymeric structure. For example, the most highly connected polymers were those constructed from asymmetric rods consisting of relatively large cross-linking elements interspersed with smaller elastomeric domains. In addition to providing insights into the evolution of elastomeric proteins, simulations such as those presented here may prove valuable for the tuneable design of new molecules that may be exploited as useful biomaterials.

Nonuniform Internal Structure of Fibrin Fibers: Protein Density and Bond Density Strongly Decrease with Increasing Diameter

“…Computational modeling may also provide insights into the lateral assembly of fibrin fibers. A mechanism that may result in the observed nonuniform fiber with a denser core and a less dense periphery is diffusion-limited aggregation (DLA) of rods into fibers, under the condition that the rods will not move significantly after assembly, as shown in a recent modeling paper [ 47 ]. Before activation, a fibrinogen solution is essentially a colloidal solution of noninteracting fibrinogen molecules (particles), which upon activation quickly aggregate into a fibrin network.…”

Shear structuring as a new method to make anisotropic structures from soy–gluten blends

“…WG consists of diverse proteins of which the glutenins and gliadins are the most important. The elastomeric proteins of WG, particularly the high molecular weight glutenin subunits, are able to aggregate (Lasztity, 1984;Song & Parkinson, 2012) on hydrating and mixing (Day, Augustin, Batey, & Wrigley, 2006). It was observed that WG forms fibers spontaneously on mixing with water (Zaidel, Chin, Rahman, & Karim, 2008).…”

A conceptual framework for computational models of Achilles tendon homeostasis

“…There have been many computation models developed that are relevant to tendon. Some of the most notable computational modeling achievements to date have been: tropocollagen formation into a triple helix driven by minimization of chemical potential energy; molecular dynamics model of tropocollagen load‐deformation response; discrete models of tropocollagen aggregation and the load‐deformation properties of the aggregates; discrete model of collagenase binding to a collagen fibril and the diffusing along it; continuum model of collagen fibril degradation by proteases; various composite solid, viscoelastic, and poroelastic continuum models represented the time‐dependent load‐deformation characteristics of tendon; various hyper‐elastic models representing the large deformation response of tendon, sometimes spanning a couple of length scales; hyper‐elastic damage models of tendon, that can capture strain softening; hyper‐elastic damage and repair model of tendon, capturing some aspects of structural changes within the tendon; probabilistic mechanical models that include the distribution of fiber lengths, and probabilistic damage models capturing extension‐damage behaviors …”

“…Parkinson et al developed a computational model of tropocollagen unit assembly into collagen fibrils, using up to 50,000 rod‐like particles of different configurations, and also examined the mechanical properties of the aggregates. More sophisticated models of collagen fibrils and other elastomeric proteins have been developed to model ‘aggregate assembly’, meaning collagen fibril formation …”

“…View of a section of an aggregate generated with rods composed of a single elastomeric domain of length 20 units and diameter 1 unit, using KT = 20 and X = 1000. Orange arrows indicate the direction of lateral surface diffusion for a newly accreted rod (red) that drive the minimization of exposed hydrophobic surface …”